{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:56:36Z","timestamp":1785412596051,"version":"3.56.0"},"reference-count":48,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T00:00:00Z","timestamp":1781827200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/00ca2c886","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Red de Investigaci\u00f3n Cooperativa Orientada a Resultados en Salud-Enfermedades Vasculares Cerebral","doi-asserted-by":"publisher","award":["RD24\/0009\/0028"],"award-info":[{"award-number":["RD24\/0009\/0028"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Venous thromboembolism (VTE) significantly impacts lung adenocarcinoma outcomes, yet current predictive tools lack precision. We investigated plasma extracellular vesicle (EV) mRNA as a liquid biopsy source to identify a pro-thrombotic molecular profile in VTE patients. Within a prospective cohort of 260 patients, we performed a retrospective nested case\u2013control study, matching 10 VTE cases with 11 thrombosis-free controls. Plasma EV-RNA was analyzed via high-throughput sequencing. Differentially expressed genes (DEGs) were integrated with functional enrichment and explored across public non-cancer VTE datasets, buffy coat samples, and cell lines. RNA-seq identified 483 DEGs within the VTE patient EV compartment, predominantly linked to neutrophil degranulation (NETosis), inflammation, and coagulation. We identified a set of EV-associated candidate genes (SELP, ELANE, MYL9, DNASE1L3) distinguishing cancer-associated thrombosis from non-malignant VTE, along with transcripts (TFPI, FCGR2A) selectively enriched within the EV compartment relative to circulating blood cells. P-selectin (SELP) was the only significantly increased marker, providing the strongest complementary support at the protein level. This molecular state was detectable prior to the occurrence of VTE. Plasma EVs capture a multicellular mRNA profile, reflecting the systemic immunothrombotic activation in lung adenocarcinoma. Despite sample size limitations, these findings should be considered exploratory and hypothesis-generating, but they suggest the EV-derived mRNA in combination with circulating markers such as SELP may provide a framework for future studies aimed at improving risk stratification.<\/jats:p>","DOI":"10.3390\/ijms27125558","type":"journal-article","created":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T14:37:42Z","timestamp":1781879862000},"page":"5558","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["An Immunothrombotic Extracellular Vesicle mRNA Profile Associated with Thrombosis in Lung Adenocarcinoma"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8038-972X","authenticated-orcid":false,"given":"Mar\u00eda","family":"Marcos-Jubilar","sequence":"first","affiliation":[{"name":"Hematology and Cell Therapy Area, Clinica Universidad de Navarra, 31008 Pamplona, Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria de Navarra (IdiSNA), 31008 Pamplona, Spain"},{"name":"Red de Investigaci\u00f3n Cooperativa Orientada a Resultados en Salud (RICORS)-Cerebrovascular Diseases, Instituto Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-2866-0590","authenticated-orcid":false,"given":"Clara","family":"Fernandez-Arias","sequence":"additional","affiliation":[{"name":"Hematology and Cell Therapy Area, Clinica Universidad de Navarra, 31008 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-0249-4249","authenticated-orcid":false,"given":"Carmen","family":"Herrero-Carrasco","sequence":"additional","affiliation":[{"name":"Hematology and Cell Therapy Area, Clinica Universidad de Navarra, 31008 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0547-681X","authenticated-orcid":false,"given":"Elizabeth","family":"Guruceaga","sequence":"additional","affiliation":[{"name":"Bioinformatics Platform, CIMA-University of Navarra, 31008 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karmele","family":"Valencia","sequence":"additional","affiliation":[{"name":"Program in Solid Tumors, Cancer Division, Cancer Center Cl\u00ednica Universidad de Navarra (CCUN), CIMA-University of Navarra, 31008 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pablo","family":"Elizalde","sequence":"additional","affiliation":[{"name":"Hematology and Cell Therapy Area, Clinica Universidad de Navarra, 31008 Pamplona, Spain"},{"name":"Red de Investigaci\u00f3n Cooperativa Orientada a Resultados en Salud (RICORS)-Cerebrovascular Diseases, Instituto Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susana","family":"Inoges","sequence":"additional","affiliation":[{"name":"Hematology and Cell Therapy Area, Clinica Universidad de Navarra, 31008 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8850-8866","authenticated-orcid":false,"given":"Ram\u00f3n","family":"Lecumberri","sequence":"additional","affiliation":[{"name":"Hematology and Cell Therapy Area, Clinica Universidad de Navarra, 31008 Pamplona, Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria de Navarra (IdiSNA), 31008 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6300-7670","authenticated-orcid":false,"given":"Josune","family":"Orbe","sequence":"additional","affiliation":[{"name":"Hematology and Cell Therapy Area, Clinica Universidad de Navarra, 31008 Pamplona, Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria de Navarra (IdiSNA), 31008 Pamplona, Spain"},{"name":"Red de Investigaci\u00f3n Cooperativa Orientada a Resultados en Salud (RICORS)-Cerebrovascular Diseases, Instituto Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2390200","DOI":"10.1080\/07853890.2024.2390200","article-title":"Incidence and risk factors of VTE in lung cancer: A meta-analysis","volume":"56","author":"Yang","year":"2024","journal-title":"Ann. 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